Your Digest for Thursday, Mar 07, 2024 11:59 PM


Prolonged PPIs should be discontinued after the acute episode as they can precipitate hepatic encephalopathy. (Uptodate)

Prevention of rebleeding


[!TIP] Mnemonic: LADA -> L for "LATE" diagnosis Type 1


Pompholyx

pompholyx.png
Dishydrotic eczema
Precipitated by sweat - in high humidity conditions.
pruritic (intensely)
Small blisters
Management

Tinea

Tinea capitis - causes scarring alopecia;
caused by Trichophyton tonsurans (in UK and US) or microsporum canis (from dogs)
microsporum causes green glow under Wood's light.
Requires systemic antifungal therapy because topical do not penetrate the hair shaft.

Tinea corporis is caused by Trichophyton rubrum and Trichophyton verrucosum (from cattle)


Diagnosis of Diabetes mellitus

DMDiagnosticCriteria.png

[!TIP]Mnemonic: Seven - eleven
DiabetesSevenElevenMnemonic.png
HbA1C > 6.5% is diagnosis of DM.

HbA1C should be avoided in pregnancy, children, haemoglobinopathies, haemolytic anaemia, HIV, untreated iron deficiency anaemia. (due to high turnover)
Abnormally low HbA1c can be caused by deteriorating renal function and weight loss.


System effect
CVS Increase cardiac ouput ( increased heart rate, contractility, stroke volume); Peripheral resistance drops; pulse pressure increases; Decreases diastolic BP (hypothyroidism causes diastolic hypertension Source
RS Maintains respiratory drive
GI increases motility
Blood Incr. 2,3-DPG - increased oxygen unloading
Muscles Increase speed of muscle contraction
Increases the density of beta receptors in skeletal muscle (and adipose tissue) Source
Carbs Increase gluconeogenesis, glycolysis and glycogenolysis, intestinal glucose absorption, cellular glucose reabsorption. (Thyroxine increases glucagon and insulin secretion) overall effect is hyperglycemia.
Due to ⬆ rate of absorption, post prandial hyperglycemia occurs which resolves rapidly.
lipid PL and TGL + increased cholesterol turnover (patients lose weight), increased liver LDL receptors (see below) Lipolysis, increased serum free fatty acids (which can be oxidised), decreased serum cholesterol,
Lipid cont.
Proteins Anabolism Source but at high doses, catabolism.
Sympathetic NS Increases expression of beta adrenergic receptors and in heart decreases alpha receptors. See Perissive effect below:
At cellular level Thyroid hormones No. of mitochondria, increase activity of Na/K ATPase -> thermogenesis, increaes Na and K condutivity
Sexual function hypothyroidism in women -> menorrhagia or oligomenorrhea, decreased libido in men and women.

Types of Thyroiditis

Thyroiditis typically causes a painful goiter.

Hashimoto thyroiditis (chronic autoimmune thyroiditis)

hashimotosThyroiditis.png

Post partum thyroiditis.


#2021SBR-NOV/Q05
#2016GM-APR/Q22


📑Azathioprine


- Or with a *differentiating agent*. (**All trans retinoic acid**)
- has the t(15:17) translocation.

Background physiology of lymphocytes

LymphocyteOrigin.png
Source-YouTube
Source-YouTube
Source-YouTube

MHC I MHC II
Present on ALL nucleated cells Presenton APCs
Binds CD8 receptor Binds CD4 receptors
Stimultes Cytotoxic T cells Stimulates T helper cells
Details on T cells: Source

Natural killer cells

[!TIP] 2 minute summary: from MSD manuals
Chronic myeloid leukemia (CML) occurs when a pluripotent stem cell undergoes malignant transformation and clonal myeloproliferation, leading to a striking overproduction of mature and immature granulocytes. Initially asymptomatic, CML progression is insidious, with a nonspecific “benign” stage (malaise, anorexia, weight loss) eventually giving way to accelerated or blast phases with more ominous signs, such as splenomegaly, pallor, easy bruising and bleeding, fever, lymphadenopathy, and skin changes. Peripheral blood smear, bone marrow aspirate, and demonstration of the Philadelphia chromosome are diagnostic. Treatment is with tyrosine kinase inhibitors (TKI) such as imatinib, dasatinib, nilotinib, bosutinib, and ponatinib, which significantly improve response and prolong survival. Myelosuppressive drugs (eg, hydroxyurea), stem cell transplantation, and interferon alfa are also sometimes used.

| Polycythemia | ❗Anaemia - may be symptomatic | |
| | Lymphadenopathy - only in blast crisis | |
| ❗Trilineage hypercellularity | Bone marrow : increased cellularity | |
| Mx : Aspirin and phlebotomy | TKI - b / intenstive chemotherapy like AML if blast phase occurs | |

Chronic lymphocytic leukemia features

[!INFO] 2 minute summary from MSD manuals.
Chronic lymphocytic leukemia (CLL) is characterized by progressive accumulation of phenotypically mature malignant B lymphocytes. Primary sites of disease include peripheral blood, bone marrow, spleen, and lymph nodes. Symptoms and signs may be absent or may include lymphadenopathy, splenomegaly, hepatomegaly, fatigue, fevers, night sweats, unintentional weight loss, and early satiety. Diagnosis is by flow cytometry and immunophenotyping of peripheral blood. Treatment is delayed until symptoms develop and generally involves chemotherapy and immunotherapy. However, treatments are evolving, and first-line regimens may include targeted agents such as inhibitors of Bruton tyrosine kinase (Btk) and Bcl-2, with or without chemotherapy. CLL is considered incurable with current treatment.


Protozoan parasite.

The center of the spectrum consists of localized cutaneous leishmaniasis (LCL), which is the most common clinical presentation.
At the opposite end of the spectrum, diffuse cutaneous leishmaniasis (DCL) is caused by polyparasitic disease with a predominance of parasitized macrophages and no granulomatous inflammation.
This is the commonest form in Sri Lanka. Source
CutaneousLeishmaniaisSriLanka.png
CutaneousLeishmaniasis.png


| Amantadine | Enhances dopamine release | Modest effect - used in advanced disease to improve diskinesia | |


MODY -> Young patient (so looks like T1DM) but has strong family history -> MODY
MODY -> MONOGENIC -> 'modhi' -> leader -> Autosomal dominant


[!INFO] mnemonic: V - ONE - Constriction
V2 for "tube" - collecting duct.
(DDAVP = desmopressin)

[!INFO] Terlipressin is far better than vasopressin than for variceal bleeds.


1/3 of patients have cirrhosis at presentation!
The good news is that 80% go into remission with treatment.

It will show interface hepatitis and chronic active hepatitis.
Drug therapy is not indicated in all.

The 2 major indications for measuring C-peptide levels include

[!INFO] Causes of hyperinsulinemic-hypoglycemia with elevated C peptide
A C-peptide level is very useful in the differential diagnosis since it is only elevated with a

  1. beta cell tumor - Nesidiobalstosis (there is no distinct tumour but the pancreatic duct epithelium diffusely contains insulin secreting cells)
  2. insulinoma
  3. and sulfonylurea therapy (and ? meglitinides)

Other causes for hyperinsulinemic-hypoglycemia

  1. Insulin autoantibody syndrome : insulin binds to autoatibodies and is then sporadically released leading to hypoglycemia with normal C-peptide levels.
    1. About half of such patients report exposure to carbimazole or methimazole.
      Type B insulin resistance caues hyperinsulinaemia but not hypoglycemia:
    2. Type B insulin-resistance is a more clinically severe form of disease caused by the production of antibodies targeting the insulin receptor
    3. Type A insulin-resistance is caused by a mutation in the insulin receptor gene INSR, and is thus inherited (5).

[!INFO] what is a mast cell?
See -> [[Haematopoiesis lineages.png]]
Mast cells are derived from myeloid progenitors.
They are released into the blood as immature progenitors.
From the blood, they migrate to tissues which border the external environment. (skin, gut and respiratory mucosa etc).
They are long lived, tissue dwelling cells.
They secrete many inflammatory mediators when activated by a antigen which crosslinks the mast cell receptors which are membrane bound IgE.
mastCellReceptors.png
Source

See [[General Pharmacology#Prostaglandin and COX pathway]] -> [[overviewEicosanoidsLeukotrienes.png]]

See Source for T cell cytokines.

TNF and IL-1 are produced by activated macrophages, mast cells, endothelial cells, generated in response to bacterial toxins, T cell stimulation, and immune complexes.

  1. mitochondrial or intrinsic pathway => promoted by DNA damage and accumulation of misfolded proteins. Pro apoptotic proteins leak out of the mitrochondria; This pathway is inhibited when the cell receives growth signals. This pathway involves P53 protein. (It's protein, TP53, is a tumour suppressor gene).
    1. See [[importanceOfP53.png]] Source
  2. Death receptor (extrinsic) pathways => Involved in apoptosis of self reactive lymphocytes and in cell death triggered by cytotoxic T lymphocytes.
  3. apoptoticPathways.png

TNF is produced by tissue macrophages that are responding to a pathogen.
TNF is pro inflammatory:

In acute inflammation, neutrophils predominate from 6-24 hours. Then monocytes arrive from 24-48 hours.
TNF and IL-1, in addition to local effects, have systemic effects;
They trigger the acute phase response.
Histamine

Serotonin - (discovered as a substance in serum (sero) which causes vasoconstriction (tonin)


IgA nephropathy
(Berger disease)
Henoch-Schonlein (IgA vasculitis) Goodpasture Xn ANCA positive vasculitis
Young people Children
rare over age > 20;
30 and 50 year peaks Older patients
IgA based immune complex mediated nephropathy Primary (IgA) Immune complex mediated Small vessel vasculitis Anti basement membrane antibodies Pauci immune vaculitis
No pulmonary haemorrhage Diffuse alveolar haemorrhage rare; commoner if HSP occursin adults / adolescents Diffuse alveolar haemorrhage + Life threatening alveolar haemorrhage
- - 1. pulmonary h'rage
2. RPGN
1. pulmonary h'rage
2. RPGN
purpura - purpura + (with normal PLT count) purpura - purpura of lower extremities
IgA deposition in mesangium; mesangial proliferation
Granular deposits
Identical to IgA nephropathy.
? most likely granular deposits
Linear antibody deposition in kidney;
IgG mediated -> complement activation -> c5a mediated neutrophil damage.
Pauci immune
Recurrences common upto 1/3 show recurrencs Recurrences rare maintenance therapy continued for 2 to 3 years.
Respiratory symtoms due to URTI 1-2 day before no significant respiratory symptoms (but CXR may show some changes) Respiratory symptoms due to alveolar haemorrhaging; may precede renal symptoms by months. Otitis, bloody nasal discharge, crusting. (i.e sinusitis or epistaxis)
Mesangial proliferation; mesangial proliferation upto crescent formation. Renal biopsy identical to IgA nephropathy RPGN - crescents mild focal glomerulonephritis upto crescent formation
40% develop CKD -> slow to progress Self limiting in children;
more severe clinical course in adults.
Will develop CKD if delayed presentation / management
ACEi/ ARB and immunosuppresion as last line Supportive management +/- steroids IvIG and Immunosuppresion Immunosuppresion required for all; induction and maintenance phases.
maintenance therapy continued for 2 to 3 years.

Follicular cells give rise to Papillary, follicular and anaplastic CA.
Parafollicular C cells -> Medullary CA. (C cells are neuroendocrine cells and they produce [[Hormone Physiology#Calcitonin|Calcitonin]]).

Most cold nodules are due to benign processes (>90%)
Cold nodules have an approximately 5% risk of being cancerous.
--- simplified to--->

[!TIP] mnenonic: hurthel - turtle
Turtle cells have polygonal markings -> polygonal cells seen on histology
hurthlecellMnemonic.png

Hürthle cell carcinoma is a rare, more agrressive variant of follicular carcinoma. 5 year survival is 50 - 60%.
Composed of distinct looking polygonal cells with acidophillic cytoplasm.
thyroidCAanaplasticMedullaryMnemonic.png
So much so that there is a clinical distinction between identification of patients with familial MTC and diagnosis a new sporadic MTC.
RET proto-oncogene mutations are seen in all MTC syndromes.

Approximately 80% of individuals with a RET genetic variant will develop medullary thyroid cancer at some point in their lives.

In treatment of MEN, to avoid intra op hypertension, resection of pheochromocytoma should be done before MTC resection.
පර පා පි
පර මේ ෆි
මා මේ ෆි
[!TIP] Mnemonic: A for anaplastic and abyssmal
Occurs in older adults (60-70) -> older adult with a thyroid nodule could have a dangerous thyroid CA.
1 year survival is a dismal 20%. Median survival is 5-6 months.

Suspect in a middle aged woman with pruritus who has elevated ALP and possibly other autoimmune conditions.
ALP is the only abnormal investigation
But Fatigue is a prominent presenting symptom. Pruritus is an early and common sign. Icterus is a late sign.



overviewEicosanoidsLeukotrienes.png


The most commonly involved organ is the lung, followed by the skin - UpToDate

  1. Kidneys - can cause rapidly progressing AKI with necrotizng glomerulonephritis (haematuria, proteinuria or normal ufr)
  2. Myocarditis can occur leading to cardiac failure.

[!INFO] Domains in MELD
9.57 × loge (creatinine) + 3.78 × loge (total bilirubin) + 11.2 × loge (INR) + 6.43.


Mnemonic for HLA types and associations

HLA-A3:
3 looks like E.
AE - haemochromatosis

HLA-B51 - (B52 was a bomber in WW2)
behcetsHLAB51Mnemonic.png
diseases beging with B.
Behcet's disease

HLA-B27 - B 2 -> b is the second letter, A is the first leter.
All A's
Anki spondi
Arthrits - reactive and psoriatic
Anterior uveitis

HLA-DR2 (DR - doctor) 2 for two disease
Goodpasture
narcolepsy
(Good doctor is sleeping)

HLA-DR3 (3 looks like E)
Dry Eyes - Sjogrens - And everything starts with an S
Snakes - dermatitis herpetiformis (herpetologist - "herpet" means to do with snakes)
PBC - Seerrhosis

HLA-DR4
T1DM
Rheuamtoid arthritis (4 looks like A - RA -arthritis)

Glaucoma

Source Youtube
Managementof AACG - acetazolamid 500mg stat followed by pilocarpine
POAG - primary open angle glaucoma - associated with myopia (long eye ball) and not hypermetropia (short eye ball) like AACG.
Cup : Disk ratio > 0.7 is seen.
mechanismPapilloedema.png